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Biochemical Profilingnof the Brain and Blood Metabolomenin a Mouse Model of Prodromal Parkinson’s Disease Reveals DistinctnMetabolic Profiles 前驱帕金森病小鼠模型的大脑和血液代谢组的生化分析揭示了不同的代谢特征

Figshare Pub Date : 2018-05-25 DOI: 10.1021/acs.jproteome.8b00224.s001

Stewart F. Graham (710687), Nolwen L. Rey (5284559), Ali Yilmaz (1430095), Praveen Kumar (8242), Zachary Madaj (5284568), Michael Maddens (5284571), Ray O. Bahado-Singh (804903), Katelyn Becker (5284565), Emily Schulz (5284574), Lindsay K. Meyerdirk (5284562), Jennifer A. Steiner (157109), Jiyan Ma (300432), Patrik Brundin (3880)

{"title":"Biochemical Profilingnof the Brain and Blood Metabolomenin a Mouse Model of Prodromal Parkinson’s Disease Reveals DistinctnMetabolic Profiles","authors":"Stewart F. Graham (710687), Nolwen L. Rey (5284559), Ali Yilmaz (1430095), Praveen Kumar (8242), Zachary Madaj (5284568), Michael Maddens (5284571), Ray O. Bahado-Singh (804903), Katelyn Becker (5284565), Emily Schulz (5284574), Lindsay K. Meyerdirk (5284562), Jennifer A. Steiner (157109), Jiyan Ma (300432), Patrik Brundin (3880)","doi":"10.1021/acs.jproteome.8b00224.s001","DOIUrl":"https://doi.org/10.1021/acs.jproteome.8b00224.s001","url":null,"abstract":"Parkinson’sndisease is the second most common neurodegenerativendisease. In the vast majority of cases the origin is not genetic andnthe cause is not well understood, although progressive accumulationnof α-synuclein aggregates appears central to the pathogenesis.nCurrently, treatments that slow disease progression are lacking, andnthere are no robust biomarkers that can facilitate the developmentnof such treatments or act as aids in early diagnosis. Therefore, wenhave defined metabolomic changes in the brain and serum in an animalnmodel of prodromal Parkinson’s disease. We biochemically profilednthe brain tissue and serum in a mouse model with progressive synucleinopathynpropagation in the brain triggered by unilateral injection of preformednα-synuclein fibrils in the olfactory bulb. In total, we accuratelynidentified and quantified 71 metabolites in the brain and 182 in serumnusing <sup>1</sup>H NMR and targeted mass spectrometry, respectively.nUsing multivariate analysis, we accurately identified which metabolitesnexplain the most variation between cases and controls. Using pathwaynenrichment analysis, we highlight significantly perturbed biochemicalnpathways in the brain and correlate these with the progression ofnthe disease. Furthermore, we identified the top six discriminatorynmetabolites and were able to develop a model capable of identifyingnanimals with the pathology from healthy controls with high accuracyn(AUC (95% CI) = 0.861 (0.755–0.968)). Our study highlightsnthe utility of metabolomics in identifying elements of Parkinson’sndisease pathogenesis and for the development of early diagnostic biomarkersnof the disease.","PeriodicalId":522527,"journal":{"name":"Figshare","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147898738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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